Sugar alcohols derived from six-carbon sugars (otherwise known as hexitols), such as, for example, sorbitol, mannitol, iditol and galactitol, have been long known. Particularly in recent years, significant interest has been expressed in the possible use of the internal dehydration products of such materials to displace petroleum-based materials in a number of commercially important applications. Dianhydrohexitols such as isosorbide, isomannide and isoidide, as made by the acid-catalyzed removal of two water molecules from the original internal structure of the corresponding hexitol, have been used or proposed for use in place of petroleum-based monomers such as terephthalic acid, for instance, though particularly in the case of isosorbide a substantial number of additional uses have been, are being or are envisaged to be developed.
As related in U.S. Pat. No. 7,122,661 and in U.S. Pat. No. 8,008,477, however, it has heretofore generally been required for the majority of these uses to apply a purification treatment to the compositions resulting directly from the dehydration step, as these compositions will typically contain each of the stereoisomers isosorbide, isomannide and isoidide, as well as less dehydrated materials such as sorbitan, mannitan and iditan, a variety of oxidation or degradation products, oligomeric and polymeric byproducts and various other “highly coloured species of a poorly defined nature”, see, e.g., U.S. Pat. No. 8,008,477 at column 2, line 35.
As summarized in the aforementioned U.S. Pat. No. 7,122,661 and U.S. Pat. No. 8,008,477, a number of approaches had been suggested previously for obtaining the internal dehydration products (and particularly for obtaining the dianhydrohexitols such as isosorbide especially) in greater purity, for a variety of reasons. Some of these approaches sought improvements in purity through changes to the dehydration process by which the dianhydrohexitols are made, while other approaches involved a form of purification after the dianhydrohexitol compositions are formed.
For example, GB 613,444 describes the production of an isosorbide composition through dehydration carried out in a water/xylene medium, followed by distillation and recrystallization from an alcohol/ether mixture.
WO 00/14081 describes distillation and recrystallization from a lower aliphatic alcohol, or distillation alone in the presence of sodium borohydride and in an inert atmosphere.
U.S. Pat. No. 4,408,061 uses gaseous hydrogen halide or liquid hydrogen fluoride dehydration catalysts with carboxylic acid cocatalyst followed by distillation of the crude isosorbide or isomannide compositions thus obtained.
U.S. Pat. No. 4,564,692 briefly mentions prepurification on “ion exchangers and/or activated charcoal”, followed, after concentration by evaporation and seeding of crystals of the desired isohexide, by crystallization from water.
Rather than modifying conventional acid-catalyzed dehydration methods or using different, often costly techniques to clean up the direct products of such methods as in the above references, it has also been proposed to generate the dianhydrohexitols by means of certain bimetallic catalysts in the presence of hydrogen. For example, EP 380,402 describes synthesis of the dianhydrohexitols by reacting sugar alcohols with hydrogen under pressure and in the presence of particular catalysts based on a combination of copper and a noble metal or gold.
U.S. Pat. No. 6,013,812 observes, however, that these catalysts tended to lose activity fairly rapidly, and proposes an improvement to a conventional acid-catalyzed dehydration wherein acid-stable Ru, Rh, Pd and/or Pt based hydrogenation catalysts and hydrogen are used during the dehydration step. The dehydration product is said to contain “less than 1 wt % polymers”, col. 2, line 28.
U.S. Pat. No. 7,122,661 for its part describes a process for obtaining isohexide compositions of 99.5% or greater purity and having improved color and color stability on storage, without necessarily involving a comparatively costly and low yielding crystallization step from a solvent medium, through using an ion-exchange step followed by a decolorization treatment step. More particularly, a distilled isohexide composition is described as subjected to treatment with at least one ion-exchange means, which can be a mixed bed of anionic resin(s) and cationic resin(s) or a succession of cationic resin(s) and anionic resin(s), followed by treatment with at least one “decolorizing means”. The decolorizing means can be activated charcoal in granular or pulverulent form. In certain embodiments, a second treatment with the decolorizing means is contemplated before the ion-exchange treatment step. Improved stability isosorbide compositions were said to be produced by the process, though the same steps—ion-exchange treatment followed by decolorizing means treatment—were surprisingly said to result in a destabilizing effect when performed in the reverse order.
U.S. Pat. No. 8,008,477, assigned to the same owner as the '661 patent and having one of the inventors of the '661 patent as its sole named inventor, describes an alternate process for preparing a color stable isosorbide composition. According to the '477 patent, the stability of an isohexide composition is not necessarily correlated with its purity, and preparation in an inert atmosphere and/or in the presence of sodium borohydride in the dehydration or in the distillation step likewise did not materially improve the stability of these compositions, col. 3, lines 58-67. Rather, “only” the use of specific stabilizing agents in nongaseous form and after the distillation step was helpful for improving the storage stability of isohexide compositions at ambient and moderate temperatures, col. 4, lines 1-14. Suitable “stabilizing agents” are chosen from the group comprising reducing agents, antioxidants, oxygen scavengers, light stabilizers, anti-acid agents, metal-deactivating agents and mixtures of at least any two of such materials, col. 4, lines 48-53. In certain embodiments, an optional further “purification step” was taught following the distillation, an example being the use of both ion exchange and decolorizing means of the type described in the earlier '661 patent.
JP 2006/316025 for its part earlier indicated that the formation of degradation/decomposition products in aged samples of isosorbide was related to auto oxidation of the 1,4-sorbitan monoanhydrohexitol side product and to unspecified “side reactions” involving a solvent (such as water and organic solvents such as xylene and toluene) from the dehydration of sorbitol to make isosorbide. The JP'025 reference prescribes multiple distillations of the crude isosorbide in the absence of a solvent at gradually increasing temperatures and/or at least one such solventless distillation followed by thermal treatment of the isosorbide to reduce the 1,4-sorbitan content of the isosorbide product, with bleaching of the isosorbide product included in each case by treating with ion exchange resins and carbon adsorption.
While the JP'025 reference does thus appreciate that degradation and color formation can proceed from the 1,4-sorbitan monoanhydrohexitol side product, neither the JP'025 reference nor the '477 patent appears to appreciate that the degradation pathways are as extensive as we have found or the corresponding degradation products and unstable intermediate species as numerous as we have found, as elaborated below. Not surprisingly, we have found that the approaches taken and the corrective measures proposed by the '477 patent and the JP'025 reference are correspondingly incomplete or even counterproductive.